LEAPS-MPS: Surface Morphological Effect on Biomolecular Attachment to Responsive Microgels for Tunable Biomimetic 3D-Cell Culture Scaffolds

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。细胞外基质是一种由蛋白质、矿物质和生物分子组成的3d生物复合网络，支持周围组织中细胞功能的生化和结构需求。生物技术专家面临的一个重要挑战是开发合成的3d生物复合支架，以模仿细胞外基质的天然生物材料特性，以便更有效地表征、诊断和适当治疗恶性细胞行为。本研究的未来目标是利用响应性生物相容性聚合物微凝胶网络开发仿生3D支架，这将更好地反映细胞所经历的微环境的固有3D物理化学性质。创建这些平台的第一步和本提案的主要目标是了解控制微凝胶表面功能的结构-功能关系，这是在工程3d -生物复合支架中指导目标组织中细胞行为的最重要特征之一。这项研究将为斯佩尔曼学院——黑人女性的小型文科本科院校——提供必要的机会，以有价值的本科生研究和课堂参与的形式，将高分子材料化学纳入化学和生物化学课程。重要的是，这将是本科生学习化学的一个新的基础分支的绝佳机会。参与这项研究将扩大STEM劳动力中代表性不足的群体的参与，并通过培训更多的专业人员来解决代表性不足和服务不足的人群中出现的社会问题，从而使社会受益。技术摘要：该提案支持未来的研究目标，即创建可调的多功能仿生3d细胞培养支架，通过理解控制响应性微凝胶上反应性官能团与靶生物分子之间的生物分子表面附着的界面参数，来确定控制病变组织中集体细胞行为的机制。响应性微凝胶是一种“智能”胶体水凝胶颗粒，可以根据外部刺激（pH值、温度、离子强度）调整其大小、形态和物理性质。生物材料通过生物分子识别介导特异性细胞反应和指导新组织的形成，通过生物活性分子的化学或物理方法实现表面和体积修饰。核心假设是，化学生物分子与反应性微凝胶的附着是由微凝胶孔隙度和微凝胶中活性官能团的可及性决定的，这些因素可能导致未来微凝胶基生物复合材料的介观结构和形态发生深刻变化。本提案描述了验证该假设的实验方法，其中生物分子附着浓度将根据结构不同的微凝胶表面的聚合物段密度进行研究。这项工作的具体目的是确定1)微凝胶孔隙度和2)活性官能团可及性对生物分子附着密度和分布的影响。本研究将为研究表面结构对生物分子附着、后表面功能化化学的影响提供新的认识。这些发现将有助于多功能杂交生物材料的合理开发，包括用于组织工程和治疗部位特异性药物递送的仿生3d细胞培养支架。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).Nontechnical Abstract:The extracellular matrix is a 3D-biocomposite network of proteins, minerals, and biomolecules that support the biochemical and structural requirements for cell function in surrounding tissues. An important challenge for biotechnologists has been to develop synthetic 3D-biocompsite scaffolds that mimic the native biomaterial properties of the extracellular matrix, so that malignant cell behaviors can be more effectively characterized, diagnosed, and properly treated. The future goal for this research is to develop biomimetic 3D-scaffolds from responsive biocompatible polymer microgel networks, which will better reflect the indigenous 3D physical chemical properties of the microenvironment that cells experience. The first step toward creating these platforms and the primary objective of this proposal is to understand the structure-function relationships that govern microgel surface functionality, one of the most important features for directing cell behavior in target tissues among the engineered 3D-biocompsite scaffold. This research will provide the necessary opportunity for Spelman College – small liberal arts undergraduate institution of Black women – to incorporate polymer materials chemistry into the chemistry & biochemistry curriculum, in the form of meritorious undergraduate research and classroom engagement. Importantly, it will be a prime opportunity for undergraduate students to learn a new and foundational branch of chemistry. Participation in this research will broaden participation of underrepresented groups in the STEM workforce and benefit society by training more professionals to address emerging societal problems across more underrepresented and underserved communities of people.Technical Abstract:This proposal supports the future goal for the research program of creating tunable, multifunctional biomimetic 3D-cell culture scaffolds for determining the mechanisms that govern collective cell behavior in diseased tissues by understanding the interfacial parameters that govern biomolecular surface attachment between reactive functional groups on responsive microgels and target biomolecules. Responsive microgels are “smart” colloidal hydrogel particles that can adapt their size, morphology, and physical properties in response to an external stimulus (pH, temperature, ionic strength). Biomaterials mediate specific cellular responses and direct new tissue formation via biomolecular recognition, achieved by surface and bulk modification via chemical or physical methods with bioactive molecules. The central hypothesis is that chemical biomolecular attachment to responsive microgels is governed by microgel porosity and the accessibility of the reactive functional groups in the microgel, and that these factors can lead to profound changes in the mesostructure and morphology of future microgel-based biocomposites. This proposal describes the experimental approach for verifying the hypothesis, where biomolecular attachment concentration will be investigated according to the polymer segment density of structurally diverse microgel surfaces. The specific aims of the proposed work are to identify the role that 1) microgel porosity and 2) reactive functional group accessibility imparts on biomolecular attachment density and distribution. This research will provide new knowledge on the influence that surface structure has on biomolecular attachment, post surface functionalization chemistry. These findings will contribute towards the rational development of multifunctional hybrid biomaterials, including biomimetic 3D-cell culture scaffolds for tissue engineering and theranostic site-specific drug delivery.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.